International Journal of Pharmaceutics 393 (2010) 219–229 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Pharmaceutical Nanotechnology Chitosan–magnesium aluminum silicate nanocomposite films: Physicochemical characterization and drug permeability Wanwisa Khunawattanakul a , Satit Puttipipatkhachorn b , Thomas Rades c , Thaned Pongjanyakul a,∗ a Faculty of Pharmaceutical Sciences, Khon Kaen University, 123 Mittraphap Road, Khon Kaen 40002, Thailand b Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand c School of Pharmacy, University of Otago, PO Box 913, Dunedin, New Zealand article info Article history: Received 11 January 2010 Received in revised form 16 March 2010 Accepted 8 April 2010 Available online 14 April 2010 Keywords: Chitosan Magnesium aluminum silicate Nanocomposite film Heat treatment Drug permeability abstract Chitosan–magnesium aluminum silicate (CS–MAS) films were prepared and the effects of MAS content and heat treatment of the CS–MAS dispersion before film casting on the physicochemical and drug perme- ability properties of the films were investigated. CS could interact with MAS via electrostatic interaction and intermolecular hydrogen bonding mechanisms, resulting in nanocomposite formation, for which it was not necessary to apply the heat treatment on the composite dispersions. The nature of the exfoliated and intercalated nanocomposite films formed was depended on the MAS content added. The heat treat- ment on the composite dispersions caused an increase in tensile strength, but reduced %elongation of the CS–MAS nanocomposite films. The exfoliated nanocomposite films showed higher flexibility, water uptake, and drug permeability compared to the CS and intercalated CS–MAS nanocomposite films. At higher MAS content, the CS–MAS films prepared using heat treatment had a lower water uptake, resulting in lower drug permeability when compared with those prepared using non-heated dispersions. The per- meation mechanism of non-electrolyte and negatively charged drugs across the CS–MAS nanocomposite films was predominantly controlled by diffusion in water-filled microchannels, whereas both adsorption onto MAS and diffusion processes occurred concurrently for the film permeation of positively charged drugs. The findings of this study suggest that CS–MAS nanocomposite films can be formed without heat- ing of the composite dispersion before casting. CS–MAS nanocomposites showed strong potential to be used as a film former for coated tablets intended for modulating drug release. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Chitosan (CS) is a polysaccharide that consists of N-acetyl-d- glucosamine and d-glucosamine. CS is insoluble at neutral and alkaline pH since its pK a is in the range of 6.2–7.0 (Hejazi and Amiji, 2003). It dissolves and swells in acidic media due to ionization of the amino groups of the CS molecules. CS has been extensively used in many fields, e.g. agriculture, water and waste treatment, food and beverages, cosmetics, and pharmaceutics (Rinaudo, 2006), due to its biodegradability, biocompatibility, and non-toxicity (Illum, 1998). In the field of pharmaceutics, CS has been used as an excip- ient, e.g. as film forming agent and gelling agent. Additionally, CS provides controlled-release properties to drugs and has been used in the preparation of tablets (El-Kamel et al., 2002), beads (Anal and Stevens, 2005), microspheres (Hejazi and Amiji, 2002), gels (Senel et al., 2000), and films (Remu ˜ nán-López et al., 1998; Senel et al., 2000). ∗ Corresponding author. Tel.: +66 43 362092; fax: +66 43 202379. E-mail address: thaned@kku.ac.th (T. Pongjanyakul). Due to its positive charge, CS is able to interact with negatively charged clay, which has a silicate layer structure. When CS disper- sions were mixed with clays, the zeta potential of clays and the viscosity of the composite dispersion were changed (Günister et al., 2007; Khunawattanakul et al., 2008). The dry material obtained from these composite dispersions is called nanocomposite if CS intercalates into the silicate layer of the clay (Alexandre and Dubois, 2000). Different type of clays, such as montmorillonite (Darder et al., 2003, 2005; Wang et al., 2005), magidiite (Liu et al., 2007), and rectorite (Wang et al., 2006, 2007), have all be used to pre- pare nanocomposite materials with CS. In the preparation process of these materials, it is necessary to use a heat treatment on the composite dispersion to induce the formation of nanocomposites (Darder et al., 2003, 2005; Wang et al., 2005). Furthermore, the clay content influenced thermal stability and mechanical properties of the nanocomposites (Wang et al., 2005). CS–clay nanocomposites were developed and characterized for use as biosensors (Fan et al., 2007; Zhao et al., 2008), packaging materials (Rhim et al., 2006), and superabsorbent materials (Ruiz-Hitzky et al., 2005). Moreover, CS–clay films could retard the release of a bioactive agent incorpo- rated into the films (Wang et al., 2007). 0378-5173/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2010.04.007